Attenuation of the Activation of NLRP3 Inflammasome in Fibroblast Like Synoviocytes of Rheumatoid Arthritis by Baicalin through Regulating the Let-7i-3p/PI3K/Akt/NF-κB Signaling Axis

[Objectives]To study the effect and mechanism of baicalin on the activation of NLRP3 inflammasome in human fibroblast like synoviocytes of rheumatoid arthritis(HFLS-RA).[Methods]To confirm that baicalin alleviated the activation of NLRP3 inflammasome in HFLS-RA,the expression of NLRP3 before and after baicalin treatment was observed by immunofluorescence.Western blot was used to detect the protein expression of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1 after baicalin treatment for 48 h,and the contents of IL-1 and IL-18 in the supernatents were detected by ELISA.In order to explore the mechanism of baicalin alleviating the activation of NLRP3 inflammasome,the corresponding relationship between let-7i-3p and PIK3CA was verified by double luciferin and Westen blot analysis.The expression of let-7i-3p and PI3K before and after baicalin intervention was detected by RT-qPCR.let-7i-3p interference was used to verify whether baicalin mitigated the activation of enhanced NLRP3 inflammasome.[Results]Baicalin(50 and 100 mg/L)significantly reduced the activation of NLRP3 inflammasome,inhibited the protein expressions of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1,and the secretion of IL-1 and IL-18.let-7i-3p and PIK3CA had a targeted correspondence,and baicalin up-regulated the expression of let-7i-3p and down-regulated the expression of PIK3CA.Baicalin attenuated the activation of NLRP3 inflammasome enhanced by let-7i-3p interference.[Conclusions]Baicalin can up-regulate let-7i-3p expression,inhibit PI3K/Akt/NF-κB signal transduction,and thus reduce the activation of NLRP3 inflammasome in HFLS-RA.

Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis

Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.

Development of biomedical hydrogels for rheumatoid arthritis treatment

Rheumatoid Arthritis(RA)is an autoimmune disorder that hinders the normal functioning of bones and joints and reduces the quality of human life.Every year,millions of people are diagnosed with RA worldwide,particularly among elderly individuals and women.Therefore,there is a global need to develop new biomaterials,medicines and therapeutic methods for treating RA.This will improve the Healthcare Access and Quality Index and also relieve administrative and financial burdens on healthcare service providers at a global scale.Hydrogels are soft and cross-linked polymeric materials that can store a chunk of fluids,drugs and biomolecules for hydration and therapeutic applications.Hydrogels are biocompatible and exhibit excellent mechanical properties,such as providing elastic cushions to articulating joints by mimicking the natural synovial fluid.Hence,hydrogels create a natural biological environment within the synovial cavity to reduce autoimmune reactions and friction.Hydrogels also lubricate the articulating joint surfaces to prevent degradation of synovial surfaces of bones and cartilage,thus exhibiting high potential for treating RA.This work reviews the progress in injectable and implantable hydrogels,synthesis methods,types of drugs,advantages and challenges.Additionally,it discusses the role of hydrogels in targeted drug delivery,mechanistic behaviour and tribological performance for RA treatment.

Synergistic chemotherapy/PTT/oxygen enrichment by multifunctional liposomal polydopamine nanoparticles for rheumatoid arthritis treatment

Amultifunctional liposomal polydopamine nanoparticle(MPM@Lipo)was designed in this study,to combine chemotherapy,photothermal therapy(PTT)and oxygen enrichment to clear hyperproliferating inflammatory cells and improve the hypoxic microenvironment for rheumatoid arthritis(RA)treatment.MPM@Lipo significantly scavenged intracellular reactive oxygen species and relieved joint hypoxia,thus contributing to the repolarization of M1 macrophages into M2 phenotype.Furthermore,MPM@Lipo could accumulate at inflammatory joints,inhibit the production of inflammatory factors,and protect cartilage in vivo,effectively alleviating RA progression in a rat adjuvant-induced arthritis model.Moreover,upon laser irradiation,MPM@Lipo can elevate the temperature to not only significantly obliterate excessively proliferating inflammatory cells but also accelerate the production of methotrexate and oxygen,resulting in excellent RA treatment effects.Overall,the use of synergistic chemotherapy/PTT/oxygen enrichment therapy to treat RA is a powerful potential strategy.

Elucidating the therapeutic mechanism of Cang Zhu and Huang Bai in rheumatoid arthritis: a comprehensive analysis integrating network pharmacology and GEO data

In the present study, we explored the therapeutic potential of Cang Zhu-Huang Bai (CZ-HB) against rheumatoid arthritis (RA) and elucidated the associated mechanisms. The approach involved a systematic examination of the chemical ingredients of CZ-HB using TCMSP database. Subsequently, we predicted the targets corresponding to the active ingredients through the SwissTargetPrediction database. We constructed a comprehensive drug-ingredient-target network using Cytoscape (v 3.8.0), with the main ingredients of the drugs identified based on their degree values. We conducted a meticulous search across GEO, GeneCards, Therapeutic Target Database (TTD), and PharmGkb databases to identify target proteins associated with RA. The intersection of targets corresponding to the drugs' active ingredients and those associated with RA provided crucial insights. Functional analysis, including GO and KEGG pathway enrichment analyses, was performed on the intersecting targets using R (v 4.2.2). Additionally, a protein-protein interaction (PPI) network of the intersecting targets was constructed using the String platform. The resulting drug-ingredient-target-disease topology network was visualized using Cytoscape (v 3.8.0), and the Cytohubba plugin facilitated the identification of hub genes. The study revealed 35 active ingredients of CZ-HB and their corresponding 673 targets. We identified 14 major active ingredients crucial to the drug’s effects by focusing on the degree values. Furthermore, our investigation uncovered 784 targets associated with RA. Through the intersection of drug and disease targets, we pinpointed 34 active ingredients of CZ-HB capable of acting on 126 targets implicated in RA. The topological network analysis of the intersected genes identified five hub genes. The binding affinity of these hub genes to the 14 primary active ingredients of the drug was confirmed through molecular docking. The enrichment results of the intersecting genes suggested that CZ-HB exerted its anti-RA effects through a multi-component, multi-target, and multi-pathway approach.

Altered Iron-Mediated Metabolic Homeostasis Governs the Efficacy and Toxicity of Tripterygium Glycosides Tablets Against Rheumatoid Arthritis

Rheumatoid arthritis(RA),a globally increasing autoimmune disorder,is associated with increased disability rates due to the disruption of iron metabolism.Tripterygium glycoside tablets(TGTs),a Tripterygium wilfordii Hook.f.(TwHF)-based therapy,exhibit satisfactory clinical efficacy for RA treatment.However,drug-induced liver injury(DILI)remains a critical issue that hinders the clinical application of TGTs,and the molecular mechanisms underlying the efficacy and toxicity of TGTs in RA have not been fully elucidated.To address this problem,we integrated clinical multi-omics data associated with the anti-RA efficacy and DILI of TGTs with the chemical and target profiling of TGTs to perform a systematic network analysis.Subsequently,we identified effective and toxic targets following experimental validation in a collagen-induced arthritis(CIA)mouse model.Significantly different transcriptome–protein–metabolite profiles distinguishing patients with favorable TGTs responses from those with poor outcomes were identified.Intriguingly,the clinical efficacy and DILI of TGTs against RA were associated with metabolic homeostasis between iron and bone and between iron and lipids,respectively.Particularly,the signal transducer and activator of transcription 3(STAT3)–hepcidin(HAMP)/lipocalin 2(LCN2)–tartrate-resis tant acid phosphatase type 5(ACP5)and STAT3–HAMP–acyl-CoA synthetase long-chain family member 4(ACSL4)–lysophosphatidylcholine acyltransferase 3(LPCAT3)axes were identified as key drivers of the efficacy and toxicity of TGTs.TGTs play dual roles in ameliorating CIA-induced pathology and in inducing hepatic dysfunction,disruption of lipid metabolism,and hepatic lipid peroxidation.Notably,TGTs effectively reversed“iron–bone”disruptions in the inflamed joint tissues of CIA mice by inhibiting the STAT3–HAMP/LCN2–ACP5 axis,subsequently leading to“iron–lipid”disturbances in the liver tissues via modulation of the STAT3–HAMP–ACSL4–LPCAT3 axis.Additional bidirectional validation experiments were conducted using MH7A and AML12 cells to confirm the bidirectional regulatory effects of TGTs on key targets.Collectively,our data highlight the association between iron-mediated metabolic homeostasis and the clinical efficacy and toxicity of TGT in RA therapy,offering guidance for the rational clinical use of TwHF-based therapy with dual therapeutic and toxic potential.

Crossroads:Pathogenic role and therapeutic targets of neutrophil extracellular traps in rheumatoid arthritis

Rheumatoid arthritis(RA)is a prevalent autoimmune disease whose main features include chronic synovial inflammation,bone destruction,and joint degeneration.Neutrophils are often considered to be the first responders to inflammation and are a key presence in the inflammatory milieu of RA.Neutrophil extracellular traps(NETs),a meshwork of DNA-histone complexes and proteins released by activated neutrophils,are widely involved in the pathophysiology of autoimmune diseases,especially RA,in addition to playing a key role in the neutrophil innate immune response.NETs have been found to be an important source of citrullinated autoantigen antibodies and inflammatory factor release,which can activate RA synovial fibroblasts(FLS)and cause joint damage.This article reviews the role of NETs in the pathophysiology of RA,demonstrating the application of multiple molecules with various therapies,with a view to informing the discovery and development of novel biomarkers and therapeutic targets for RA.

Clinical and experimental investigations into the immune modulatory effects of Qianjinba polysaccharides on a rheumatoid arthritis mouse model:in vivo and in vitro studies

Qianjinba is derived from the dried root of a legume vine and is known for its plant polysaccharide,which has demonstrated anti-inflammatory,analgesic,and neuroprotective properties.Despite these known effects,its immunomodulatory potential remains underexplored.This study aimed to investigate the immunoregulatory effects of Qianjinba polysaccharide(QJBDT)in a murine model of rheumatoid arthritis(RA)and elucidate its mechanism of action in inhibiting the disease.To assess the immunomodulatory effects,RAW264.7 macrophage cells were stimulated with bacterial lipopolysaccharide(LPS)and subsequently treated with varying concentrations of QJBDT or total glucoside of paeonic acid(TGP).Cell proliferation and the expression levels of mitogen-activated protein kinase p38 and nuclear factor NF-κB proteins were evaluated.Following the successful modeling of RA in mice,different doses of QJBDT and TGP were administered via intragastric administration once daily for 21 d.Mice were divided into normal,model,QJBDT low-,medium-,and high-dose groups,along with a positive control group(TGP group),each comprising 10 mice.Organ coefficients were calculated,immune indexes in blood cells were determined,and alterations in T helper cell 17(Th17)and regulatory T cells(Treg)were analyzed using flow cytometry.Compared to the normal group,cell proliferation rates significantly increased across all groups(P<0.05).Elevated expressions of p38 and NF-κB proteins were observed in the model group,QJBDT low-and medium-dose groups(P<0.05).Various systemic immune inflammation indexes,including systemic immune inflammation index(SII),total inflammation systemic index(AISI),and systemic inflammation response index(SIRI),platelet-to-lymphocyte ratio(PLR),neutrophil-to-lymphocyte ratio(NLR),monocyte-to-lymphocyte ratio(MLR),showed increments(P<0.05).Additionally,body weight and organ coefficients of the thymus,spleen,and liver decreased in both the model and low-dose groups(P<0.05).Moreover,Th17 levels increased while Treg levels decreased across all groups(P<0.05),resulting in a heightened Th17 to Treg ratio in the model and low-dose groups(P<0.05).Notably,the QJBDT medium-dose,high-dose,and positive control groups demonstrated significant inhibitory effects on cell proliferation compared to the model group(P<0.05),along with reduced expression levels of p38 and NF-κB(P<0.05).Furthermore,various immune indicators from routine blood tests exhibited different degrees of decrease(P<0.05),while immune indices displayed increases(P<0.05).The low-,medium-,and high-dose groups of QJBDT,as well as the positive control group,showed decreased Th17 levels,elevated Treg levels,and diminished Th17 to Treg ratios(P<0.05).Additionally,there was no statistically significant difference in efficacy between the QJBDT high-dose and TGP groups(P>0.05).In conclusion,this study demonstrated that QJBDT exerted potent immunomodulatory effects on RA in mice in a dose-dependent manner.Its mechanism of action might involve the inhibition of NF-κB activation by suppressing the p38 MAPK signaling pathway.

Concomitant atypical knee gout and seronegative rheumatoid arthritis:A case report

BACKGROUND Gout and seronegative rheumatoid arthritis(SNRA)are two distinct inflammatory joint diseases whose co-occurrence is relatively infrequently reported.Limited information is available regarding the clinical management and prognosis of these combined diseases.CASE SUMMARY A 57-year-old woman with a 20-year history of joint swelling,tenderness,and morning stiffness who was negative for rheumatoid factor and had a normal uric acid level was diagnosed with SNRA.The initial regimen of methotrexate,leflunomide,and celecoxib alleviated her symptoms,except for those associated with the knee.After symptom recurrence after medication cessation,her regimen was updated to include iguratimod,methotrexate,methylprednisolone,and folic acid,but her knee issues persisted.Minimally invasive needle-knife scope therapy revealed proliferating pannus and needle-shaped crystals in the knee,indicating coexistent SNRA and atypical knee gout.After postarthroscopic surgery to remove the synovium and urate crystals,and following a tailored regimen of methotrexate,leflunomide,celecoxib,benzbromarone,and allopurinol,her knee symptoms were significantly alleviated with no recurrence observed over a period of more than one year,indicating successful management of both conditions.CONCLUSION This study reports the case of a patient concurrently afflicted with atypical gout of the knee and SNRA and underscores the significance of minimally invasive joint techniques as effective diagnostic and therapeutic tools in the field of rheumatology and immunology.

Anti-inflammatory Effect of Polysaccharide from Embelia parviflora Wall.on Rheumatoid Arthritis in Rats

[Objectives]To investigate the anti-inflammatory effect of Embelia parviflora Wall.polysaccharide on rheumatoid arthritis(RA)in rats.[Methods]RA rat model was induced by type II collagen.After successful modeling,the rats were divided into model group,positive group,low,medium and high dose of E.parviflora Wall.polysaccharide groups,and normal control group.Body mass,toe volume and arthritis index were measured,and thymus index and spleen index were calculated.The levels of interleukin-1β,interleukin-6 and tumor necrosis factor-αin serum and synovial tissue of ankle joint were detected by ELISA.[Results]Compared with the normal control group,the pathological changes such as synovial hyperplasia and unclear layer were observed in the model group,the body mass was decreased(P<0.05),the toe volume,arthritis index,thymus and spleen index were increased(P<0.05),and the levels of IL-1β,IL-6 and TNF-αin serum and ankle synovial tissue were increased(P<0.05).Compared with the model group,the histopathological changes in synovium of ankle joint in the positive group and the medium and high dose groups of E.parviflora Wall.polysaccharide were significantly improved,and the body mass was increased(P<0.05).The toe volume,arthritis index,thymus index and spleen index were decreased(P<0.05).The levels of IL-Iβ,IL-6 and TNF-αin serum and synovial tissue of ankle joint were increased(P<0.05),while there was no significant difference between the low dose group of E.parviflora Wall.polysaccharide and the model group(P>0.05).[Conclusions]E.parviflora Wall.polysaccharide can reduce the body's inflammatory response and improve RA,which may be related to the inhibition of the activation of inflammatory cytokines IL-1β,IL-6 and TNF-α.

Interleukin 6 and Bone Erosions in Rheumatoid Arthritis in an African Hospital

Introduction: Rheumatoid arthritis (RA) is a chronic, erosive and deforming inflammatory rheumatic disease. In the era of biotherapies and the arrival of biosimilars in sub-Saharan Africa, the objective of this study was to describe plasma IL-6 variations in RA patients at Cité Verte District Hospital (Cameroon). Material and Methods: Descriptive and analytical cross-sectional study from December 1, 2021 to May 31, 2022. We included patients over 18 years old suffering from RA (ACR/EULAR 2010). Patients with an infection were not included. The data collected were age, sex, smoking status, family history, disease duration, disease activity by DAS28, CRP, rheumatoid factor, and plasma level of IL-6. Bone erosion was sought on radiography and ultrasound. Result: We included 31 patients, 25 of whom were women (80.6%). The mean age was 47.27 ± 17.97 years. Disease activity was predominantly moderate (32.3%) and severe (32.3%). Mean IL-6 level was 15.29 ± 2.36 pg/ml (extremes: 11.26 pg/ml and 20.15 pg/ml). IL-6 levels were higher in patients with a history of smoking. Similarly, IL-6 levels were higher in patients with mildly active RA in remission than in moderately and severely active RA. Mean IL-6 levels were significantly higher in patients with erosive RA (16.3 pg/ml VS 14.6 pg/ml). Conclusion: IL-6 levels were significantly elevated in men, weaned smokers and patients with bone erosions.

Evaluating the influence of a structured nursing protocol on targeted outcomes in rheumatoid arthritis patients

Objective:Rheumatoid arthritis(RA)requires comprehensive management.Structured nursing protocols may enhance outcomes,but evidence is limited.This study evaluated the effect of a structured nursing protocol on RA outcomes.Materials and Methods:In this one-group pre-post study,30 Egyptian RA patients completed assessments before and after a 12-week nursing protocol comprising education,psychosocial support,and self-management promotion.Assessments included clinical evaluation of joint counts,erythrocyte sedimentation rate(ESR),and C-reactive protein(CRP)and patient-reported Arthritis Self-Efficacy Scale(ASES),Health Assessment Questionnaire(HAQ),Visual Analog Scale(VAS)for pain,and Hospital Anxiety and Depression Scale(HADS).Results:The study demonstrated significant improvements in both clinical-and patient-reported outcomes.Joint count decreased from 18.4±4.2 to 14.2±3.8(P<0.001),ESR from 30.1±6.8 mm/h to 25.5±6.8 mm/h(P<0.01),and CRP levels from 15.2±3.6 mg/L to 11.8±2.9 mg/L(P<0.01)postintervention.Patient-reported outcomes showed a marked increase in ASES score from 140±25 to 170±30(P<0.001)and reductions in HAQ from 1.6±0.4 to 1.3±0.3(P<0.01),VAS pain score from 7.8±1.7 to 6.2±1.2(P<0.001),and HADS anxiety and depression scores from 11±3 to 8±2(P<0.05)and 10±2 to 7±1(P<0.05),respectively.Conclusion:A structured nursing protocol significantly improved clinical disease activity,physical functioning,pain,self-efficacy,and emotional well-being in RA patients.A multifaceted nursing intervention appears beneficial for optimizing RA outcomes.

Correlation Analysis Between Changes of D-Dimer Level and Rheumatoid Arthritis Complicated with Interstitial Lung Disease

Objective:To explore the correlation between the change of D-dimer level and rheumatoid arthritis complicated with interstitial lung disease.Methods:From January 2022 to February 2024,20 rheumatoid arthritis patients complicated with interstitial lung disease(interstitial lung disease group),20 rheumatoid arthritis patients without interstitial lung disease(without interstitial lung disease group),and 20 healthy people(control group)in Xijing Hospital were selected for this study.The fasting venous blood of the three groups of subjects was collected and their D-dimer,C-reactive protein(CRP),rheumatoid factor(RF),and erythrocyte sedimentation rate(ESR)were detected.Subsequently,the correlation between each index and rheumatoid arthritis complicated with interstitial lung disease was analyzed.Results:The D-dimer level of the interstitial lung disease group was significantly higher than the other two groups(P<0.05).The D-dimer level of the group without interstitial lung disease was significantly higher than the control group(P<0.05).CRP levels in the interstitial lung disease group and the group without interstitial lung disease were significantly higher than those of the control group(P<0.05).The ESR and RF levels of the interstitial lung disease group were significantly higher than the other two groups(P<0.05).The levels of ESR and RF levels of the group without interstitial lung disease were significantly higher than the control group(P<0.05).Conclusion:D-dimer levels of rheumatoid arthritis patients are higher than those of healthy individuals,and those complicated with interstitial lung disease present even higher levels.This finding shows that there is a correlation between D-dimer levels and rheumatoid arthritis with interstitial lung disease,which may facilitate the evaluation and diagnosis of this disease.

Correlation Study Between T Lymphocyte Subsets and Rheumatoid Arthritis

Objective:To study the effect of Helicobacter pylori infection on rheumatoid arthritis and T-lymphocyte subpopulations in patients with rheumatoid arthritis and to provide a new method for the treatment of rheumatoid arthritis by removing Helicobacter pylori from patients.Methods:60 patients with rheumatoid arthritis admitted to the hospital from May 2022 to May 2023 were selected for the study,and all patients underwent a 13-carbon urea breath test to detect gastric H.pylori and the test results showed that 20 cases were negative and 40 cases were positive.The 40 positive patients were divided into the treatment group(n=20)and non-treatment group(n=20)by random number table method and the treatment group was given anti-Helicobacter pylori treatment,and the non-treatment group was given maintenance rheumatoid basic treatment,comparing the anti-cyclic citrulline peptide(CCP),DS28 score,peripheral blood T-lymphocyte subsets(CD4^(+)T-lymphocytes,CD8^(+)T-lymphocytes,CD4^(+)/CD8^(+)ratio)before and after the treatment of patients by 13-carbon urea respiration test(pylori-negative group,20 patients)and those who were positive for the treatment of H pylori(pylori-positive group,40 patients).Besides,the correlation of peripheral blood T-lymphocyte subsets and disease activity between treatment and non-treatment groups in the pylori-positive group was identified together with the correlation of DS28 scores,TNF-αlevels,sedimentation and immunoglobulin,lymphocyte subsets in the pylori-positive treatment group and positive non-treatment group as well as the level of globulin,lymphocyte subsets,and peripheral blood lymphocytes before and after treatment.Results:Before treatment,CCP,DS28 score,CD8^(+)T lymphocyte level of the pylori-negative group were lower than that of the positive group,and CD4^(+)T lymphocyte and CD4^(+)/CD8^(+)ratio were higher than that of the positive group(P<0.05);after treatment,the indexes of the pylori-positive group improved,and there was no significant difference in the comparison of the indexes with those of the pylori-negative group(P>0.05);the positive treatment group had a DS28(3.19±1.02)points,positive non-treatment group DS28(5.36±1.85)points,non-treatment group DS28 score and CD4^(+)T lymphocytes,CD4^(+)/CD8^(+)negative correlation with CD8^(+)T lymphocytes showed a positive correlation(P<0.05);before the treatment,pylori-positive treatment group and non-treatment group DS28 scores,TNF-αlevels,peripheral blood T lymphocyte subpopulation levels were not significantly different(P>0.05);after treatment,DS28 score,TNF-αlevel,CD8^(+)T of the treatment group were lower than those of the non-treatment group,and CD4^(+)T lymphocytes and CD4^(+)/CD8^(+)ratio were higher than those of the non-treatment group(P<0.05).Conclusion:H.pylori affects the level of T lymphocyte subsets in patients with rheumatoid arthritis,and there is a certain correlation between the two.Removal of H.pylori can improve the level of T lymphocyte subsets,which is important for the treatment of patients with rheumatoid arthritis.

Research progress of local characteristic drugs for treatment of rheumatoid arthritis in Xinjiang

Rheumatoid arthritis(RA)is a systemic autoimmune disease characterized by synovitis.This disease tends to recur,persist,and is difficult to cure.The pathogenesis of RA is complex.Currently,the commonly used treatments for RA—non-steroidal anti-inflammatory drugs(NSAIDs),disease-modifying anti-rheumatic drugs(DMARDs),glucocorticoids,and immunosuppressants—have notable side effects with long-term use and may be ineffective for some patients.Therefore,it is crucial to find drugs with limited side effects and significant curative effects.Xinjiang's local characteristic drugs have a long history,abundant resources,and are known for their safety and effectiveness in treating RA.In recent years,many studies have reported on the mechanisms of action and therapeutic effects of Xinjiang's local characteristic drugs on RA.This article reviews the pathogenesis of RA,as well as the research progress and treatment characteristics of Xinjiang-featured drugs.

Rare Association between Chronic Tophaceous Gout and Rheumatoid Arthritis in a Black African Subject: A Case Report

Rheumatoid arthritis (RA) and gout are common diseases, but their coexistence is rare. We describe the case of a 76-year-old man with hypertension who had been treated for gout for 20 years on allopurinol and colchicine. He was seen in consultation for deforming polyarthritis of the small and large joints, which had been evolving for about 2 years. The acute episode occurred 10 days earlier with the onset of bilateral and symmetrical polyarthritis affecting the large and small joints. The physical examination revealed a peripheral joint syndrome with ulnar gale force deformities of the hands and several buttonhole deformities of the fingers. In addition, there were nodules, some of which were fistulised, giving rise to a chalky slurry. The biology revealed an inflammatory syndrome in addition to rheumatoid factors and ACPA, which were elevated. Biological analysis of the nodular fluid revealed clusters of sodium urate crystals and ultrasound scans of the joints revealed a double-contour appearance in several joints. The diagnosis of RA was made using the 2010 ACR/EULAR criteria. The patient was treated as an outpatient with corticosteroids before being put on methotrexate. It is important to understand that these two conditions can occur at the same time, so it is important to consider them when treating patients with gout or RA.

Pleuro-Pericardial Inflammation and Effusion: A Rare Acute Initial Presentation of Rheumatoid Arthritis

Background: Rheumatoid arthritis is a systemic inflammatory arthritis characterized by joint pain and morning stiffness. The affected joints are typically symmetrically affected, and given the inflammatory nature of this condition, patients often present with warmth and erythema around affected joints as well as fatigue. Extra-articular manifestations, especially pleuro-pericardial inflammation, are rare initial presentations, although may be seen in advanced or undertreated disease. Case Presentation: We describe a case of a rheumatoid arthritis presenting atypically in a middle-aged male who came to the emergency department complaining of diffuse muscle pain and swelling in the distal extremities. Cardiac ultrasound revealed pleuro-pericardial inflammation and effusions. Myositis and infectious causes were ruled out and bilateral hand x-rays did not show erosions or any evidence of arthritic changes. All rheumatological auto-antibodies were negative except for rheumatoid factor and anti-cyclic citrullinated peptide (CCP) and a diagnosis of rheumatoid arthritis was made. The patient was started on prednisone with excellent response. Conclusions: This case highlights that rheumatoid arthritis can uncommonly present initially with extra-articular manifestations that are often manifested in advanced disease. Typically, extra-articular manifestations, especially those as severe as this patient’s, occur with untreated, advanced disease and could accompany extensive arthritic joint changes. Thus, it is important to have an understanding of rare, atypical presentations of rheumatoid arthritis so that a high index of suspicion can be maintained to make the diagnosis and initiate treatment in a timely manner.

Major depressive disorders in patients with inflammatory bowel disease and rheumatoid arthritis

BACKGROUND Various immune-mediated inflammatory diseases consisting of inflammatory bowel disease(IBD)and rheumatoid arthritis(RA),are found to have a substantial societal burden,increased healthcare costs,and progressive disability.Studies suggest that patients with vs without comorbid depression have a more significant disability,a lower likelihood of remission,and reduced adherence to therapy.Elevated interleukin(IL)-1β,tumor necrosis factor-α,and IL-6 contribute to developing depression by the impaired physiological responses to stress,resulting in increased pain,fever,fatigue,and lack thereof of interest,and thus poor long-term outcomes.This study emphasizes the timely recognition of the prevalence of major depressive disorder(MDD)in patients with RA and IBD combined,thus preventing disability.AIM To identify the prevalence level and temporal trends of depression in hospitalized IBD-RA patients.METHODS All adult hospitalized patients from January 2000 to December 2019 in the nationwide inpatient sample(NIS)were captured.The study population included all patients with a primary or secondary IBD-RA overlap disease using corresponding international classification of diseases(ICD)-9 and ICD-10 codes.IBD includes Crohn’s disease and ulcerative colitis.The study population was divided into IBD-RA without MDD(controls)and IBD-RA with MDD(cases).For group comparison between MDD vs no MDD,we used Student’s t-test for continuous variables and RaoScott Chi-square tests for categorical variables.For univariate analyses,we used logistic regression,and for multivariate analysis,we used a weighted multi-level mixed-effects model.We attested all hypotheses with two-tailed significance level of 0.05(P<0.05 was considered significant).The outcome is to examine the temporal trends and prevalence of depression in patients with IBD-RA by gender,race,and age.RESULTS A total of 133315 records were identified with IBD-RA overlap,of which 26155 patients(19.62%)had MDD.Among the IBD-RA patients,those who had MDD were younger[mean age of 56 years(SD±15)]to IBD-RA without MDD patients with a P<0.0001,more females(80%among cases vs 73%among controls)than males with a P<0.0001,frequent in the white race(79%among cases vs 73%among controls)than black race.Over the 19 years,the number of patients with MDD in IBDRA increased from 153(the year 2000)to 2880(the year 2019)in weighted NIS,representing a 1782%increase compared to the year 2000 with a P<0.001.Factors associated with higher MDD included younger age,female gender,white race,alcohol,opioids,esophageal disorders,peptic ulcer disease,chronic pancreatitis,paralysis,dementia,menopausal disorders,obesity,nutritional deficiencies,diabetes mellitus with chronic complications,and osteoarthritis.CONCLUSION There is a rise in the prevalence of depression in younger patients with IBD-RA combined compared to their counterparts.These patients are also at higher risk for the increased cost of care and poor treatment compliance.It is crucial to educate the involved clinicians to identify the early signs and symptoms of depression in patients with IBD or RA or IBD-RA combined and treat them to have a better overall prognosis.

An intra-articular injectable phospholipids-based gel for the treatment of rheumatoid arthritis

Rheumatoid arthritis(RA)is a chronic inflammatory and destructive arthropathy with a high deformity rate.Despite numerous studies and clinical trials,no curative treatment is available for large weight-bearing joints.Intra-articular(IA)injections could deliver high concentrations of drug to the afflicted joint and improve the drug efficacy while reducing systemic toxicity.However,free drugs are rapidly cleared from synovial fluid and do not significantly halt the progression of joint disease.Herein,a phospholipids-based controlledrelease gel was prepared for sustained IA delivery of celastrol(CEL)and the therapeutic efficiencywas evaluated in a rheumatoid arthritis rabbitmodel.The CEL-loaded gel(CEL-gel)contained up to 70%phospholipids yetwas easy to inject.After injecting into the joint cavity,CEL-gel achieved sol to gel phase transition without special stimuli and gelling agent.In vitro release and in vivo pharmacokinetic studies evidenced the stable and sustained release action of CEL-gel.A single IA injection of CEL-gel could maintain therapeutic efficiency for about 25 d and showed much better anti-arthritic efficacy compared to repeated injections of free drug solution(CEL-sol).Furthermore,the IA injection of CEL-gel greatly reduced the systemic toxicity of CEL.With good biocompatibility and biodegradability,CEL-gel might be a promising IA drug delivery system.

Difficult-to-treat rheumatoid arthritis treated with Abatacept combined with Baricitinib:A case report

BACKGROUND Sporadic cases of rheumatoid arthritis(RA)due to unsatisfactory responses to Abatacept(ABT)have been reported;however,the rescue therapy has not been finalized.Here,we present a case with difficult-to-treat RA(D2T RA)that was resistant to either a single ABT or a Janus kinase(JAK)inhibitor(Tofacitinib),but improved with a combination of ABT and JAK inhibitor(Baricitinib,BAT).CASE SUMMARY A 46-year-old Chinese woman who had RA for ten years that was resistant to Tocilizumab,Etanercept,Adalimumab,and ABT.According to the European League Against Rheumatism definition,the patient was diagnosed with D2T RA.It was then improved with a combination of ABT and a JAK inhibitor BAT.CONCLUSION ABT combined with BAT may be an acceptable strategy for treating D2T RA.